Cerebral effects of glucagon‐like peptide‐1 receptor blockade before and after <scp>Roux‐en‐Y</scp> gastric bypass surgery in obese women: A proof‐of‐concept resting‐state <scp>functional MRI</scp> study

Duinkerken, Eelco van; Bernardes, Gabriel; Bloemendaal, Liselotte van; Veltman, Dick J.; Barkhof, Frederik; Mograbi, Daniel C.; Gerdes, Victor E. A.; Deacon, Carolyn F.; Holst, Jens J.; Drent, Madeleine L.; Diamant, Michaëla; Kulve, Jennifer Ten; IJzerman, Richard G.

doi:10.1111/dom.14233

Cited by 9 publications

(10 citation statements)

References 36 publications

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“…Few studies have looked at the relationship between GLP-1 signaling and the default mode network. One study compared the effects of GLP-1R blockade before and after Roux-en-Y gastric bypass (RYGB) surgery and found increased functional connectivity in the default mode network post-RYGB, compared to pre-RYGB 73 . Collectively, these findings suggest that both alcohol and GLP-1 interact with the default mode network in the brain.…”

Section: Discussionmentioning

confidence: 99%

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Farokhnia

Fede

Grodin

et al. 2022

Sci Rep

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Growing evidence suggests that the glucagon-like peptide-1 (GLP-1) system is involved in mechanisms underlying alcohol seeking and consumption. Accordingly, the GLP-1 receptor (GLP-1R) has begun to be studied as a potential pharmacotherapeutic target for alcohol use disorder (AUD). The aim of this study was to investigate the association between genetic variation at the GLP-1R and brain functional connectivity, according to the severity of alcohol use. Participants were 181 individuals categorized as high-risk (n = 96) and low-risk (n = 85) alcohol use, according to their AUD identification test (AUDIT) score. Two uncommon single nucleotide polymorphisms (SNPs), rs6923761 and rs1042044, were selected a priori for this study because they encode amino-acid substitutions with putative functional consequences on GLP-1R activity. Genotype groups were based on the presence of the variant allele for each of the two GLP-1R SNPs of interest [rs6923761: AA + AG (n = 65), GG (n = 116); rs1042044: AA + AC (n = 114), CC (n = 67)]. Resting-state functional MRI data were acquired for 10 min and independent component (IC) analysis was conducted. Multivariate analyses of covariance (MANCOVA) examined the interaction between GLP-1R genotype group and AUDIT group on within- and between-network connectivity. For rs6923761, three ICs showed significant genotype × AUDIT interaction effects on within-network connectivity: two were mapped onto the anterior salience network and one was mapped onto the visuospatial network. For rs1042044, four ICs showed significant interaction effects on within-network connectivity: three were mapped onto the dorsal default mode network and one was mapped onto the basal ganglia network. For both SNPs, post-hoc analyses showed that in the group carrying the variant allele, high versus low AUDIT was associated with stronger within-network connectivity. No significant effects on between-network connectivity were found. In conclusion, genetic variation at the GLP-1R was differentially associated with brain functional connectivity in individuals with low versus high severity of alcohol use. Significant findings in the salience and default mode networks are particularly relevant, given their role in the neurobiology of AUD and addictive behaviors.

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Section: Discussionmentioning

confidence: 99%

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Farokhnia

Fede

Grodin

et al. 2022

Sci Rep

View full text Add to dashboard Cite

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“…RYGB surgery also increases precuneus BOLD response to low fat/sugar food cues while decreasing response to high fat/sugar food cues [46]. Finally, weight loss and decreased appetite for sweet and fat foods after RYGB surgery coincides with reduced resting-state functional connectivity between the insula and the anterior cingulate as well as improved sensitivity of the default mode network to GLP-1R blockade [47].…”

Section: Human Studiesmentioning

confidence: 91%

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

Décarie-Spain

Kanoski

2021

Nutrients

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Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning. We integrate physiological and behavioral neuroscience studies conducted in both rodents and human to illustrate translational findings of interest for the treatment of obesity or metabolic impairments. Collectively, the literature discussed herein highlights a model where ghrelin and GLP-1 regulate food reward-motivated behaviors via both competing and independent neurobiological and behavioral mechanisms.

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“…Similar tendencies were found by Goldstone and colleagues (2016), but correlations between GLP-1 levels and anticipatory food reward responses failed to reach significance (Goldstone et al, 2016). Relatedly, before RYGB, a GLP-1 antagonist led to an increase in basal network connectivity and a decrease in functional connectivity in the frontoparietal network in patients with obesity (van Duinkerken et al, 2021). RYGB also reduced functional connectivity in the right OFC.…”

Section: Resultsmentioning

confidence: 99%

How gut hormones shape reward: a systematic review of the role of ghrelin and GLP-1 in human fMRI

Schulz

Vezzani

Kroemer

2022

Preprint

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The gastrointestinal hormones ghrelin and glucagon-like peptide-1 (GLP-1) have opposite secretion patterns, as well as opposite effects on metabolism and food intake. Beyond their role in energy homeostasis, gastrointestinal hormones have also been suggested to modulate the reward system. However, the potential of ghrelin and GLP-1 to modulate reward responses in humans has not been systematically reviewed before. To evaluate the convergence of published results, we first conduct a multi-level kernel density meta-analysis of studies reporting a positive association of ghrelin (Ncomb = 353, 18 contrasts) and a negative association of GLP-1 (Ncomb = 258, 12 contrasts) and reward responses measured using task functional magnetic resonance imaging (fMRI). Second, we complement the meta-analysis using a systematic literature review, focusing on distinct reward phases and applications in clinical populations that may account for variability across studies. In line with preclinical research, we find that ghrelin increases reward responses across studies in key nodes of the motivational circuit, such as the nucleus accumbens, pallidum, putamen, substantia nigra, ventral tegmental area, and the dorsal mid insula. In contrast, for GLP-1, we did not find sufficient convergence in support of reduced reward responses. Instead, our systematic review identifies potential differences of GLP-1 on anticipatory versus consummatory reward responses. Based on a systematic synthesis of available findings, we conclude that there is considerable support for the neuromodulatory potential of gut-based circulating peptides on reward responses. To unlock their potential for clinical applications, future studies may move beyond anticipated rewards to cover other reward facets.

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Cerebral effects of glucagon‐like peptide‐1 receptor blockade before and after Roux‐en‐Y gastric bypass surgery in obese women: A proof‐of‐concept resting‐state functional MRI study

Cited by 9 publications

References 36 publications

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

How gut hormones shape reward: a systematic review of the role of ghrelin and GLP-1 in human fMRI

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